User login
Esketamine nasal spray, combined with standard-of-care treatment, quickly improved depression symptoms and suicidal ideation, according to results of a phase 2 study published April 16 in the American Journal of Psychiatry.
In a study of 68 patients randomly assigned to either esketamine or placebo with standard-of-care treatment, patients in the treatment group had a significantly greater improvement in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 hours’ and 24 hours’ follow-up after the first dose, reported Carla M. Canuso, MD, and her coauthors.
Esketamine, a more potent sibling of ketamine, is an N-methyl-D-aspartate receptor antagonist that modulates glutamatergic transmission. It is “being developed as an intranasal formulation for treatment-resistant depression and for rapid reduction of symptoms of major depressive disorder, including suicidal ideation, in patients at imminent risk for suicide,” Dr. Canuso and her coauthors reported.
In the study, participants were assigned randomly to twice-weekly treatment with either placebo or 84 mg of intranasal esketamine (or a reduced dose of 56 mg in the event of intolerance). The study included 4 weeks of double-blind treatment followed by 8 weeks of follow-up.
Depressive and suicidal symptoms were evaluated using MADRS criteria 4 hours and 24 hours after the initial dose, on day 25, and all visits during posttreatment follow-up. Severity of suicide risk was evaluated using the Suicide Ideation and Behavior Assessment Tool.
MADRS scores were significantly improved in the esketamine group, compared with the placebo group, both 4 hours and 24 hours after initial dosing, but not at 25 days, Dr. Canuso and her colleagues reported. The esketamine group also had significantly greater improvement on the MADRS suicidal thoughts item 4 hours after first dose (P = .002), but not 24 hours after the first dose (P = .129) or at day 25 (P = .143).
The analysis also showed that, 4 hours after the first dose, 21.2% of participants in the esketamine group achieved resolution of suicide risk, compared with 9.7% for placebo patients. At 24 hours’ follow-up, 40% of esketamine patients and 6.5% of placebo patients had achieved resolution of suicide risk.
Serious adverse events (including suicidal ideation and suicide attempts) occurred in four participants in the esketamine group during the double-blind study phase. During the follow-up period, serious adverse events occurred in one patient in the treatment group and five patients in the placebo group. Other adverse events included nausea, dizziness, dysgeusia, and dissociation.
The results “may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies,” Dr. Canuso and her colleagues wrote. However, future research still is needed to evaluate the risk of dependence, they cautioned.
“Further investigation is needed to determine the rapid effect of esketamine on measures of suicidal ideation as well as the benefit of repeated esketamine dosing on symptoms of depression in this acutely ill patient population,” the authors concluded.
The investigators reported that, in addition to Dr. Canuso, several of the other authors are employed by Janssen Research and Development – and hold stock and/or stock options in Johnson & Johnson. The study was funded by Janssen Research and Development.
SOURCE: Canuso CM et al. Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.17060720.
Before ketamine is offered as a treatment option for depression or suicidal ideation, the potential risks for dependence and abuse need to be carefully evaluated, wrote Robert Freedman, MD, professor and former chair of the department of psychiatry at the University of Colorado at Denver, Aurora, and his coauthors.
“In order to obtain FDA [Food and Drug Administration] approval for marketing, phase 3 trials need to include rigorous monitoring of patients’ craving after ketamine administration and urine monitoring before each subsequent administration to detect evidence of drug seeking from other sources,” he and his coauthors wrote.
Physicians have a responsibility to try to prevent epidemics such as the opioid crisis, and preemptive research into ketamine’s addictive properties may be one way to avoid another such crisis, he added.
“It would be wise for physicians, regulatory agencies, and the pharmaceutical industry to work together preemptively to establish a suitable framework for its therapeutic use,” he wrote. “Education of the public and physicians needs to balance both potential benefits and the risk of abuse.”
Dr. Freedman did not report any relevant disclosures.
Robert Freedman, MD, and his coauthors are members of the American Journal of Psychiatry’s editorial board. Their comments came in an editorial accompanying the study (Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.18030290).
Before ketamine is offered as a treatment option for depression or suicidal ideation, the potential risks for dependence and abuse need to be carefully evaluated, wrote Robert Freedman, MD, professor and former chair of the department of psychiatry at the University of Colorado at Denver, Aurora, and his coauthors.
“In order to obtain FDA [Food and Drug Administration] approval for marketing, phase 3 trials need to include rigorous monitoring of patients’ craving after ketamine administration and urine monitoring before each subsequent administration to detect evidence of drug seeking from other sources,” he and his coauthors wrote.
Physicians have a responsibility to try to prevent epidemics such as the opioid crisis, and preemptive research into ketamine’s addictive properties may be one way to avoid another such crisis, he added.
“It would be wise for physicians, regulatory agencies, and the pharmaceutical industry to work together preemptively to establish a suitable framework for its therapeutic use,” he wrote. “Education of the public and physicians needs to balance both potential benefits and the risk of abuse.”
Dr. Freedman did not report any relevant disclosures.
Robert Freedman, MD, and his coauthors are members of the American Journal of Psychiatry’s editorial board. Their comments came in an editorial accompanying the study (Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.18030290).
Before ketamine is offered as a treatment option for depression or suicidal ideation, the potential risks for dependence and abuse need to be carefully evaluated, wrote Robert Freedman, MD, professor and former chair of the department of psychiatry at the University of Colorado at Denver, Aurora, and his coauthors.
“In order to obtain FDA [Food and Drug Administration] approval for marketing, phase 3 trials need to include rigorous monitoring of patients’ craving after ketamine administration and urine monitoring before each subsequent administration to detect evidence of drug seeking from other sources,” he and his coauthors wrote.
Physicians have a responsibility to try to prevent epidemics such as the opioid crisis, and preemptive research into ketamine’s addictive properties may be one way to avoid another such crisis, he added.
“It would be wise for physicians, regulatory agencies, and the pharmaceutical industry to work together preemptively to establish a suitable framework for its therapeutic use,” he wrote. “Education of the public and physicians needs to balance both potential benefits and the risk of abuse.”
Dr. Freedman did not report any relevant disclosures.
Robert Freedman, MD, and his coauthors are members of the American Journal of Psychiatry’s editorial board. Their comments came in an editorial accompanying the study (Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.18030290).
Esketamine nasal spray, combined with standard-of-care treatment, quickly improved depression symptoms and suicidal ideation, according to results of a phase 2 study published April 16 in the American Journal of Psychiatry.
In a study of 68 patients randomly assigned to either esketamine or placebo with standard-of-care treatment, patients in the treatment group had a significantly greater improvement in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 hours’ and 24 hours’ follow-up after the first dose, reported Carla M. Canuso, MD, and her coauthors.
Esketamine, a more potent sibling of ketamine, is an N-methyl-D-aspartate receptor antagonist that modulates glutamatergic transmission. It is “being developed as an intranasal formulation for treatment-resistant depression and for rapid reduction of symptoms of major depressive disorder, including suicidal ideation, in patients at imminent risk for suicide,” Dr. Canuso and her coauthors reported.
In the study, participants were assigned randomly to twice-weekly treatment with either placebo or 84 mg of intranasal esketamine (or a reduced dose of 56 mg in the event of intolerance). The study included 4 weeks of double-blind treatment followed by 8 weeks of follow-up.
Depressive and suicidal symptoms were evaluated using MADRS criteria 4 hours and 24 hours after the initial dose, on day 25, and all visits during posttreatment follow-up. Severity of suicide risk was evaluated using the Suicide Ideation and Behavior Assessment Tool.
MADRS scores were significantly improved in the esketamine group, compared with the placebo group, both 4 hours and 24 hours after initial dosing, but not at 25 days, Dr. Canuso and her colleagues reported. The esketamine group also had significantly greater improvement on the MADRS suicidal thoughts item 4 hours after first dose (P = .002), but not 24 hours after the first dose (P = .129) or at day 25 (P = .143).
The analysis also showed that, 4 hours after the first dose, 21.2% of participants in the esketamine group achieved resolution of suicide risk, compared with 9.7% for placebo patients. At 24 hours’ follow-up, 40% of esketamine patients and 6.5% of placebo patients had achieved resolution of suicide risk.
Serious adverse events (including suicidal ideation and suicide attempts) occurred in four participants in the esketamine group during the double-blind study phase. During the follow-up period, serious adverse events occurred in one patient in the treatment group and five patients in the placebo group. Other adverse events included nausea, dizziness, dysgeusia, and dissociation.
The results “may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies,” Dr. Canuso and her colleagues wrote. However, future research still is needed to evaluate the risk of dependence, they cautioned.
“Further investigation is needed to determine the rapid effect of esketamine on measures of suicidal ideation as well as the benefit of repeated esketamine dosing on symptoms of depression in this acutely ill patient population,” the authors concluded.
The investigators reported that, in addition to Dr. Canuso, several of the other authors are employed by Janssen Research and Development – and hold stock and/or stock options in Johnson & Johnson. The study was funded by Janssen Research and Development.
SOURCE: Canuso CM et al. Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.17060720.
Esketamine nasal spray, combined with standard-of-care treatment, quickly improved depression symptoms and suicidal ideation, according to results of a phase 2 study published April 16 in the American Journal of Psychiatry.
In a study of 68 patients randomly assigned to either esketamine or placebo with standard-of-care treatment, patients in the treatment group had a significantly greater improvement in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 hours’ and 24 hours’ follow-up after the first dose, reported Carla M. Canuso, MD, and her coauthors.
Esketamine, a more potent sibling of ketamine, is an N-methyl-D-aspartate receptor antagonist that modulates glutamatergic transmission. It is “being developed as an intranasal formulation for treatment-resistant depression and for rapid reduction of symptoms of major depressive disorder, including suicidal ideation, in patients at imminent risk for suicide,” Dr. Canuso and her coauthors reported.
In the study, participants were assigned randomly to twice-weekly treatment with either placebo or 84 mg of intranasal esketamine (or a reduced dose of 56 mg in the event of intolerance). The study included 4 weeks of double-blind treatment followed by 8 weeks of follow-up.
Depressive and suicidal symptoms were evaluated using MADRS criteria 4 hours and 24 hours after the initial dose, on day 25, and all visits during posttreatment follow-up. Severity of suicide risk was evaluated using the Suicide Ideation and Behavior Assessment Tool.
MADRS scores were significantly improved in the esketamine group, compared with the placebo group, both 4 hours and 24 hours after initial dosing, but not at 25 days, Dr. Canuso and her colleagues reported. The esketamine group also had significantly greater improvement on the MADRS suicidal thoughts item 4 hours after first dose (P = .002), but not 24 hours after the first dose (P = .129) or at day 25 (P = .143).
The analysis also showed that, 4 hours after the first dose, 21.2% of participants in the esketamine group achieved resolution of suicide risk, compared with 9.7% for placebo patients. At 24 hours’ follow-up, 40% of esketamine patients and 6.5% of placebo patients had achieved resolution of suicide risk.
Serious adverse events (including suicidal ideation and suicide attempts) occurred in four participants in the esketamine group during the double-blind study phase. During the follow-up period, serious adverse events occurred in one patient in the treatment group and five patients in the placebo group. Other adverse events included nausea, dizziness, dysgeusia, and dissociation.
The results “may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies,” Dr. Canuso and her colleagues wrote. However, future research still is needed to evaluate the risk of dependence, they cautioned.
“Further investigation is needed to determine the rapid effect of esketamine on measures of suicidal ideation as well as the benefit of repeated esketamine dosing on symptoms of depression in this acutely ill patient population,” the authors concluded.
The investigators reported that, in addition to Dr. Canuso, several of the other authors are employed by Janssen Research and Development – and hold stock and/or stock options in Johnson & Johnson. The study was funded by Janssen Research and Development.
SOURCE: Canuso CM et al. Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.17060720.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
Key clinical point: Esketamine nasal spray, combined with standard-of-care treatment, quickly improved depression symptoms and suicidal ideation.
Major finding: Patients in the esketamine treatment group had a significantly greater improvement in scores on MADRS at 4 hours and 24 hours follow-up.
Study details: A double-blind, proof-of-concept, phase 2 study of 68 patients with major depressive disorder.
Disclosures: The study was funded by Janssen Research and Development.
Source: Canuso CM et al. Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2018.17060720.